Cetyl quaternary ammonium compound



epta 3, i942 greases ClE'IBYlL QUATERNQEY All/EIWGNKUM I CQMDPQiUND Robert S. Shelton, Mariernont, @hio, assignor to Wm. S. Merrelil 1w Cincinnati,

@hio, a corporation of Delaware No Drawing.

Application August 1, 1938,

Serial No. 222,448

14-. @laims.

This invention relates to compositions of matter for controlling microorganisms, including bacteria, fungi, and the like, and/or mitigating their efiects; and more especially to compositions which possess some or all of the following properties: bactericidal, antiseptic, fungicidal, detoxifying, bacteriostatic prophylactic and to novel chemical compounds having such properties. The invention relates particularly to such compositions which possess some or all of the aforementioned properties to a marked degree. and

which comprise .a compound or compounds of the classes of tertiary and quaternary ammonium compounds. 7

Prior to my invention it has been suggested to use certain amines and quaternary ammonium compounds for bactericidal, fungicidal, and general disinfecting purposes; and it has also been v suggested that, when quaternary ammonium compounds contain, attached to the nitrogen, besides other organic radicals, at least one high molecular weight aliphatic hydrocarbon radical, such compounds may display bactericidal and fungicidal properties. Quaternary ammonium compounds pmssessing such bactericidal and fungicidal properties have been tested only to disclosed the unexpected fact that there is av marked superiority in the bactericidal properties of quaternary ammonium compounds when such compounds comprise, as one substituent on the nitrogen, a high molecular weight hydrocarbon group with at least fourteen and not more than eighteen carbon atoms and that this superiority in the bactericidal and other specified properties reaches a maximum for common types of organisms when the high molecular weight hydrocarbon group contains sixteen carbon atoms, although compounds of the class specified, highly satisfactory for the purposes of this invention,

lecular weight hydrocarbon groups having from fourteen to eighteen carbon atoms.

My experience has further shown that the effectiveness of any particular substituted ammonium compound for the purposes of my invention, as well as its comparative harmlessness in use, depends not only upon the classes or types from which the high molecular weight hydro-- carbon group is selected, but also upon the classes or types from which the low molecular weight substituents for the other hydrogen atoms of the ammonium radical are selected. This will appear more fully hereinafter. 1

Having regard to the foregoing general considerations, the invention is directed to compositions for controlling the effects of micro-organisms including bacteria, fungi, and the like, e. g., by bactericidal, antiseptic, fungicidal, detoxifying, bacteriostatic, prophylactic, etc., action, which comprise a quaternary ammonium compound or compounds of the fundamental composition above set forth and to novel chemical compounds which possess extraordinarily efficacious germicidal, antiseptic, fungicidal, detoxifying and/or bacteriostatic properties, which have a degree of solubility that permits their convenient use in the desired dilutions or concentrations and many of which are less toxic and substantially harmless in comparison with compounds of this general class heretofore available for these purposes. The invention also contemplates bactericidal, antiseptic, fungicidal, detoxifying, bacteriostatic compositions of matter composed of or comprising a soluble quaternary ammonium compound or compounds, having aforementioned fundamental composition and desired characteristics, which, in addition, possess surface tension reducing properties whereby their penetrating action is increased as, for example, when applied to the skin or any article or surface which is difficult to wet.

The quaternary ammonium compounds of the present invention, many of Which'are novel in themselves as new compositions of matter, may

be represented in their essentials by the following formula:

R R3 R2/I![\R4 in which R1 and R2 represent low molecular weight groups, especially alkyl, hydroxalkyl, amino-alkyl, alkenyl groups or substituted derivatives thereof, especially methyl, ethyl, propyl, isopropyl,

have been obtained comprising other high mobutyl, isobutyl, allyl, methylallyl groups, etc., a1-

though higher cyclo-aliphatic or heterocyclic groups may also be present, i. e., cyclohexyl or cyclopentyl groups, which may be attached directly'or through a side chain to the nitrogen atom; in which R1, R2, and 333 may be either alike or different and may be identified and/or joined together so as to form a heterocyclic ring when both ends are attached to the N atom, e. g., pyridine, piperidine, picoline, pipecoline, pyrrol, pyrrolidine, morpholine, quinoline, quinaldine, azole, thiazole, etc., or substituted derivatives thereof; in which R3 is either hydrogen or a low molecular weight group, e. g., furfuryl, tetrahydrofurfuryl, alkyl, carbethoxyalkyl, hydroxalkyl, aminoalkylor alkenyl group alike or difi'erent from R1 or R2 or may be identified width R1 and R2 as in quinolinium and pyridinium compounds; in which R4 represents a high molecular weight aliphatic hydrocarbon group, which may be saturated or unsaturated and may be a forked or a straight chain, which contains fourteen to eighteen carbon atoms, such as myristyl, cetyl, stearyl, oleyl, etc., and which may also contain substituents, for example, the hydroxyl, halogen, carbethoxy and amino groups; and in which X stands for any acid ion constituent, for example, Cl, -Br, -I, -NO3, =SO4, CO2CH3, -CH5SO3, OH, =PO4, CO2C6H5, ==CO3, -HOC5H4CO2, the dicarboxylic and tricarboxylic acids, such as tartaric and citric and fatty acids. 7 Polyvalent acid radicals may combine several similar quaternary ammonium groups of the above type into a single molecule, or one such group may be combined with the acid while remaining valences are satisfied by different positive ions or by hydrogen.

The acid ion constituent used in these compounds has a very marked influence upon the properties, and especially upon solubility, toxicity, and activity. For bactericidal purposes, I have found that in general the nitrates, sulfates, salicylates, and benzoates as well as the halides have a marked superiority in these respects.

Among the ammonium compounds which are represented in their essentials by the foregoing formula, and which possess relatively high baclericidal, antiseptic, fungicidal, detoxifying and bacteriostatic properties, are the following:

Melting point in degrees C. (not corrected) Myristyl irimethyl ammonium bromide 244-245 Cetyl-trimethyl ammonium bromide- 238-240 Cetyl-trimethyl ammonium iodide 247.5-248 Cetyl-trimethyl ammonium chloride 227 Cetyl-triethyl ammonium bromide 210-212 Cetyl-trimethyl ammonium sulfate 195-197 Cetyl-trimethyl ammonium nitrate"--- 198-205 Cetyl-trimethyl ammonium salicylate 167 Cetyl-dimethyl N-butyl ammonium bromide 46-48 Cetyl-pyridinium bromide 225-227 Cetyl-quinolinium bromide 105-109 Cetyl-trimethyl ammonium acetate---" 233-234 Cetyl-triethyl ammonium iodide 168-169 Cetyl-diallyl methyl ammonium iodide 143-145 Cetyl-methyl piperidinium iodide 165-166 Cetyl-dimcthyl carbethoxy methyl ammonium iodide 47-53 Oleyl-trimethyl ammonium bromide 225-230 Stearyl-trimethyl ammonium bromide 223-225 Cetyl-triethyl ammonium nitrate 120-122 Cetyl-trimethyl ammonium benzoate 200-204 Cetyl-inethyl piperidinium bromide 203-204 Cetyl-methyl piperidinium nitrate 105-106 three low molecular weight groups.

aaeaeoe Cetyl-ethyl morpholinium bromide 65 indefinite Cetyl-dlmethyl carbethoxy methyl ammo- Cetyl-trimethyl ammonium hydroxide 180-185 Cetyl-trimethyl ammonium tartrate Below Cetyl-trimethyl ammonium cyanide 241-245 Cetyl-diethyl ammonium iodide 78-81 The inordinate efficacy of the compounds of the present invention is exemplified by the fact that certain of these compounds have phenol coelficients of more than 1,000 as measured by the method employed by the United States Food and Drug Administration. 7 7

It will be noted that, of the compounds above listed, the majority have the cetyl group as their high molecular weight aliphatic hydrocarbon group, that is, selected from the groups containing sixteen carbon atoms. As hereinabove suggested, these compounds have been found to be of es pecially high bactericidal efilcacy.

For the three low molecular weighth hydrocarbon groups of the formula hereinabove described it has been found, in practice, that the methyl, ethyl, allyl and carbethoxy groups and their derivatives and the double ended pentamethylene chain -(CHz) 5- combined with the nitrogen atom in a piperidinium ring or an unsaturated double ended five carbon atom chain, containing alternate double and single bonds between the carbon atoms and combined with the nitrogen atom in a heterocyclic ring are especially satisfactory and, as the total molecular weight of these side chains is increased beyond these, the solubility tends to decrease. My experience has shown, moreover, that the best compounds for the purposes of my invention are those which contain not more than 10 carbon atoms in the However, as hereinabove suggested, and as shown by the compounds hereinabove listed, various hydrocarbons of both the lower molecular weight aliphatic and the lower molecular weight heterocyclic groups may be attached to each of these three linkages of the nitrogen.

It will be understood that in the tertiary amine compounds the nitrogen is pentavalent as indicated in the above formula, whereas in the amine themselves the nitrogen is tri-valent. Inasmuch as these tertiary amine compounds, e. g., salts and hydroxide, etc., as well as the quaternary ammonium compounds are analogous to the ammonium compounds, I shall consider them herein as ammonium compounds having three or four respectively of the hydrogen atoms substituted by organic groups, and I shall so refer to them.

I have found that there is advantage in using a heterocyclic substituent and especially a chain attached at both ends to the nitrogen atom of the ammonium nucleus. In this connection it may be stated that I have found heterocyclic groups such as piperidine, quinoline, morpholine, pyridine, pyrrolidine, etc., and substituted derivatives thereof, show special bactericidal and fungicidal qualities. Moreover, I have found that many of these derivatives manifest a greater bactericidal and fungicidal action than the corresponding compounds having low molecular weight alkyl derivatives with an equal number of carbon atoms in the substituent groups. Especially the piperidinium compounds exhibit unusual solubility and unusually high activity for the purposes of my invention. For example, 1 part of cetyl methyl piperidinium bromide is soluble in 6 parts water. These very desirable qualities may make it especially useful in certain compositions and for certain purposes, for example,

in various antiseptics, bactericidal and prophylactic solutions, jellies, lozenges and other vehicles. This unusual solubility was unpredictable from what has heretofore been known to those skilled in the art, especially in view of the fact that even some of the corresponding quaternary ammonium salts with lower molecular weight aliphatic hydrocarbon substituents were of comparatively low solubility.

In further regard to the low molecular weight groups on the nitrogen in these compounds of my invention it may be stated that I have found that the substitution of any of the hydrogen atoms by an aromatic hydrocarbon radical; for example, phenyl, especially when attached by an acyclic linkage, i, e., either directly attached to the nitrogen or aliphatically attached as in the case of the benzyl group, appears to have quite a deleterious efiect, reducing the bactericidal activities as to some or all types of bacteria and frequently increasing the toxicity of the compound.

It is significant that, in the above mentioned heterocyclyic compounds having a single substituent chain attached at two positions to the ammonium nitrogen, the substituent group may be of relatively high molecular weight or include a benzenoid group which otherwise would seriously impair the quality of the composition. Apparently the advantageous efiect of the heterocyclic structure counteracts the deleterious effects of the heavier and/or'benzenoid groups. Even in such cases, however, the analogous compounds which are free from benzenoid groups are as a class superior for the purposes of my invention. Thus, for example, pyridinium compounds as a class have been found superior to quinolinium compounds.

Unsaturated groups are available among the low molecular weight groups suitable for substitution in these compounds. Especially desirable among these groups are the allyl, and methylallyl. Another group which may be utilized with advantage as a low molecular weight substituent is the carbethoxy alkyl group. In particular, cetyl dimethyl carbethoxy methyl ammonium iodide has shown unusual action in that it killed Staph. aureus in a dilution of 1:48,000. This 'indicates the remarkable bactericidal qualities of acylated compounds of the type herein described. Mixed chain and heterocyclic groups, e. g., such as tetrahydrofurfuryl have also been successfully utilized as substituents in these compounds.

In general, these compositions may be used in much the same manner as any general bactericide is used and in dilutions as high as 1:90,000,

depending upon the particular micro-organisms which it is sought to kill and the particular compound used. Cetylmethyl piperidinium bromide, for example, is eifective against Staphylococcus aureus in dilutions up to '1:92,000.

They are also highly efficacious as bacteriostatic compositions, for which purpose the best of them may be utilized in dilutions more than 1 to 1,000,000 to inhibit the action and growth of bacteria which they do not kill, and thus they are useful as preservatives. Moreover, since they are comparatively nontoxic, non-staining, tasteless and odorless they should find use in pharmaceutical products, mouth washes, tooth pastes, nose drops, prophylactics; as moth, fungus or mold preventative preparations, as wellv as in general antiseptics and disinfectants for internal or external use. Various solvents, including especially water, glycol, ethyl alcohol, and mixtures thereof, and oils may be employed. Obviously other ingredients may be added, depending upon the specific intended use to be made of the final product; and it is important in this connection that the activity of these compounds is not destroyed by the presence of other ingredients, e. g., proteins and other organic compounds, which would destroy the germicidal value of most available germicides. These ingredients may include flavors, coloring matter, as well as other therapeutic, antiseptic, healing or emollient compositions. Since these compounds are highly effective in extremely high dilutions, and prevent growth of micro organisms even in dilutions far above those which will kill such micro-organisms, they are very valuable for preserving biological material, for use in adhesives, for preserving wood and clothing, and, in general, as preservatives wherever organic decomposition or putrefaction might occur. They are further advantageously used for disinfecting operating rooms, medical instruments, floors and related surfaces, utensils and clothing, particularly woolens, where their unusual wetting properties and the fact that they are not aifected by iron salts are decided advantages.

Many germicides which are highly eifective in the absence of serium are substantially inactive in the presence of serum. The compounds of the present invention, however, compare favorably with the best bactericides in respect to their activity in the presence of serum, using Staph. aureus and B. typhosus as the test organisms. In tests with these organisms, which were carried out by adding 10% by volume of sterile serum to the bactericide dilution, it was observed that the killing dilution which was completely eifective in 10 minutes of many of these compositions of my present invention was more than 1:12,000.

Also our studies indicate that these compounds are quite active at extreme hydrogen ion concentrations. It is known that many of the common germicides are completely inactivated in an alkaline solution, whereas many of the compositions of my present invention showed definite activity at a pH of 10.5, killing Staph. aureus in a dilution of more than 1:45,000. Also it has been observed that their activity is retained at a high acidity, e. g., at pH 2, where a dilution of more than 1:50,000 killed B. typhosus. The fact that these compounds are active over a fairly large range of pH makes them of great commercial value as preservatives and germicides.

Tests that have been made, especially with cetyl trimethyl ammonium bromide, show that these compounds have a remarkable detoxifying action even in fairly dilute solutions. It was obeserved, for example, that when.0.25 cc. of a 1:1,000 cetyl trimethyl ammonium bromide was added to 0.3 cc. of a standardized 1:1,000 tetanus toxin and injected subcutaneously into 325-350 gm. guinea pigs, that the animals showed no appearances of paralysis or death after 5 days observation, while the control guinea pigs when injected with 0.3 cc. of the 1:1,000 standardized tetanus toxin under the same conditions all died within 70 hours. This shows that the above described compounds have unusual detoxifying action in extremely dilute solutions so that they may at the same time be used to kill or control infection and to counteract poisons resulting from the infection. This test may be compared with other detoxifying compounds such as formaldehyde, halogen and hydroxy compounds of salicylic acid and other derivatives which show comparable detoxifying action only in high concentrations, e. g., in the neighborhood of A; per cent.

Since these compounds are compatible with calcium salts, they may be used also in dilution with very hard water without diminution of their potency. In the concentration required for disinfection and purification processes they do not injure or stain the human skin and may, therefore, be used for disinfecting the skin, particularly the hands. Furthermore, it has been observed that these compounds in dilutions of 1 to 1,000 and less have a low surface tension for the most part in the range between 30-40 dynes/cmF, thus insuring good penetration when used as skin antiseptics. They also have action as detergents, wetting agents, and many other industrial uses which add to their usefulness for certain processes even aside from their therapeutic use.

The ammonium compounds of the present invention may be used in substance as well as in solution or emulsion and, if desired, in admixture with each other and/or with other active or inert substances such as powder, ointment bases, creams, etc.

These compounds have the further advantage that they show definite bactericidal action in vegetable oils, for example, cetyl triethyl ammonium iodide 1: 1500 in olive oil showed an antiseptic 1 zone of 3-7 mm. using the standard cup plate test. It has also been observed that these compounds are soluble to a certain extent in vegetable oils, such as olive or almond oils and that the presence of a small amount of benzyl alcohol greatly increases their solubility in oil, for example, cetyl trimethyl ammonium bromide is soluble 1:100 in a solution containing benzyl alcohol, almond oil and petrolatum. Hence these compounds will be of desirable use in rendering ointment bases bactericidal, for example the common petrolatum type of ointments. In addition to their use in the oil soluble ointment type, We also find that they have decided germicidal action in water soluble jellies, for example, cetyl trimethyl ammonium bromide 1:5000 in a tragacanth base gives definite germicidal action to this type of jelly.

It is not necessary that other ingredients should be used, but generally we find that a simple water solution or tincture will be most useful as a general antiseptic.

One very valuable composition, for example, is an aqueous solution of cetyl trimethyl ammonium bromide diluted 1:1000. This may be further diluted for use in cleansing or dressing wounds for cleaning and sterilizing solution, for use as a mouth wash, etc. For hospitals and other users who prefer more concentrated solutions, e. g., to save storage space, I may supply an aqueous solution cetyl trimethyl ammonium salicylate in dilution of 1:250 or less. This latter solution is a viscous liquid and in lower dilutions approaches even a jelly condition, but for actual use these will ordinarily be diluted, e. g., with from -100 times its weight of water, so that the final solution is entirely watery.

For treating wounds and skin infections and for disinfecting instruments which are subject to rusting, a tincture is, very useful, for example,

cetyl trimethyl ammonium salicylate 1:1000 in 30-40% ethyl alcohol.

A composition very useful for mouthwash and similar purposes is a solution of cetyl trimethyl ammonium salicylate 1:10,000 in 18-20% ethyl alcohol with aromatic oils added for flavoring.

The compositions contemplated by the present invention are made conveniently by chemical methods known to those skilled in the art, for example, by reacting upon an aliphatic amine with a reactive halide of a higher molecular aliphatic hydrocarbon.

Alternatively, amines, which already contain a higher molecular aliphatic group, may be reacted with an aliphatic halide. sulfate, acetate, etc. to form the same type of ammonium salt. It has also been observed that the corresponding halides, sulfates, nitrates, salicylates, benzoates, acetates, tartrates, etc., can easily be prepared by a prolonged boiling of the iodide in an organic solvent with the corresponding salt of the alkali, alkaline earth or heavy metal. By the above reactions high molecular weight tertiary and quaternary ammonium compounds are obtained some of which are crystalline, some viscous liquids, and some wax-like substances, which, in general, depending upon the acid radicals, readily dissolve in water, forming stable, odorless, colorless and relatively non-toxic-solutions.

The following examples will serve to illustrate some methods of preparing products embodying the principles of this invention without being restricted thereto:

Example No. 1

A reaction is effected between approximately equimolar parts by weight of triethylamine (a slight excess of the triethylamine is advisable) and cetyl iodide. The reaction mixture is heated for six hours at 130 C. After cooling, the crystalline material is allowed to stand over night, filtered oil and recrystallized from alcohol, water, or warm ethyl acetate. The cetyl-triethyl ammonium iodide thus obtained forms colorless plates M. P. 1'78-1'79 C., and is sparingly soluble in water, easily soluble in hot water or alcohol. The correspondingly stearyl and myristyl and oleyl triethyl ammonium iodides may be prepared in a similar manner.

Example No. 2

The reaction is e'fiected between approximately equimolar parts by weight of trimethylamine (33% solution in MeOI-I) (a slight excess often is advisable) and cetyl bromide at room temperature. The reaction mixture is worked up as in Example No. 1, using ethyl acetate as the recrystallizing solvent. The cetyl-trimethyl ammonium bromide thus obtained forms colorless plates, melting at 235-237 C. and is readily soluble in water. Stearyl, oleyl and myristyl trimethyl ammonium bromides and iodides may be prepared in a similar manner. (Ex. 4.)

Example No. 3

Equimolar parts by weight of trimethylamine (35% solution in methyl alcohol) and cetyl chloride are heated together in a pressure flask at C. The mixture is worked up as in Example No. 1. The resulting cetyl-trimethyl ammonium chloride is a white crystalline solid, very soluble in water. Myristyl and oleyl and stearyl trimethylammonium chlorides may be prepared in a similar manner.

Example No. 4

Substantially equimolar parts by weight of cetyl iodide and of trimethylamine in 33% solution in methyl alcohol (with slight excess of the trimethylamine) are allowed to stand at room temperature. Cetyl triethyl ammonium iodide is formed which upon recrystallization from hot acetone shows a melting range 229-231 C. Stearyl and oleyl and myristyl trimethyl ammonium iodides may be prepared in a similar manner.

Example No.5

Equimolar parts of silver sulfate and cetyl trimethyl ammonium bromide are heated for ten hours in boiling alcohol. The resulting cetyl trimethyl ammonium sulfate may be separated from the silver bromide by filtration. Other salts may be formed from the halides in a similar way, e. g., salicylate, tartrate, benzoate, nitrate.

Example No. 6

1 mol of cetyl idodide and 1 mol of diallylamine are refluxed together for 6 hours. The cetyl diallyl amine hydro-iodide is filtered off and converted to cetyl diallyl amine by treatment with 50% KOH. The free amine is extracted with benzene and distilled in vacuo at 206-208 C./6

1 mol of the cetyl diallyl amine thus obtained is treated with 1.25 mols of methyl iodide at room temperature. The solid mass of cetyl diallyl methyl ammonium iodide formed is dissolved in a small amount of alcohol, precipitated with ether, filtered, dried and recrystallized from ethyl acetate. The material melted at 143-145. The corresponding chloride and bromide may be prepared in a similar way.

Example No. 7 I

Example No. 8

Cetyl bromide is allowed to stand 3-4 days at room temperature with a bimolar amount of morpholine in ether solution. The ether solution of cetyl morpholine thus obtained is. washed with water to remove unreacted morpholine and then treated with an excess of ethyl bromide and heated at 150 for 3 hours. The product when recrystallized from ethyl acetate melts at 65 C. with some decomposition. In a similar manner the corresponding pipecolinium salt may be prepared.

Example No. 9

1 mol of quinoline and 1 mol of cetyl bromide are allowed to react in a sealed tube at 100 C. The reaction mixture is poured into ether from .which a dark brown oily liquid separated. After repeated recrystallization from ethyl acetate, yellow crystals of cetyl quinolinium bromide are obtained which melt at 105-109 C.

Example No. 10

1 mol of piperidine and 1 mol of cetyl iodide are allowed to react at room temperature for 24 hours. The cetyl piperidinium hydro-iodide thus formed is converted to N-cetyl piperidine by treatment with 50% KOH. The amine is extracted with benzene and distilled in vacuo at 205-212 C./28 mm.

The N-cetyl piperidine thus obtained is treated with a slight excess of methyl iodide which reacts immediately to form a solid mass of crystals which are washed with dry ether and recrystallized from ethyl acetate. The corresponding bromide, chloride and other salts may be prepared by refluxing cetyl piperidinium iodide in alcohol with silver chloride, bromide or other corresponding salts. Cetyl methyl piperidinium salts of such acids as sulfuric, nitric and organic acids may be prepared by heating in alcohol cetyl methyl piperidinium iodide with the appropriate silver or sodium salts.

The pyrrolidinium analogs of these compounds may be prepared by the same methods.

Example No. 11

Cetyl N-butyl dimethyl ammonium bromide may be prepared from either cetyl bromide and n-butyl dimethylamine or from n-butyl bromide and cetyl dimethyl amine. Approximately 48 to 72 hours at 40 C. are sufliclent to bring about reaction. It may be recrystallized from ether and melts at 46 to 48 C.

Example No. 12

1 mol of myristyl bromide and 1.25 mols of trimethyl amine are allowed to react at room temperature for 24 hours. The crystalline mass formed by the reaction is filtered oil and recrystallized from ethyl acetate. M. P. 244-245 C.

Example No. 13

1 mol of oleyl bromide is allowed to react at room temperature with 1.25 mols of trimethylamine. The crystalline mass formed by this reaction is filtered oflz' and recrystallized from ethyl acetate. M. P. 250-230 C.

Example No. 14

1 mol of stearyl bromide is allowed to react at room temperature with 1.25 mols of trimethylamine. The resulting crystalline mass is washed with ether and recrystallized from ethyl acetate. M. P. 223-225 C.

Example No. 15

1 mol of pyridine and 1 mol of cetyl bromide are refluxed for 10 or 15 hours at the boiling point of pyridine. The reaction mixture is poured into ether from which a crystalline material separates. After repeated recrystallization :from ethyl acetate white crystals of cetyl pyridinium bromide are obtained which melt at 225-227. This material is quite soluble in water. In a similar manner the corresponding, picolinium lutidinium, and collidinium derivatives can be made.

Particular compositions disclosed in this application, including certain additional data with respect thereto, are more particularly set forth and claimed in copending applications, Serial Numbers 287,956, 287,957, 287,958, 287,959, filed August 1, 1939.

What I claim is:

1. A germ counteracting composition which 75 comprises, as the essential germ counteracting cals being free from any benzene nucleus attached to the nitrogenby acyclic linkage.

2. A composition as defined in claim 1, in which the ammonium compound is in aqueous solution.

3. A composition as defined in claim 1, in which the ammonium compound is in oil solution.

4. A composition as defined in claim 1, in which the ammonium compound is in tincture. 5. A germ counteracting composition which comprises, as the essential germ counteracting ingredient thereof, a soluble quaternary ammonium compound, the ammonium nitrogen of which has a cetyl radical, attached by one of its valence linkages and has attached by three of its valence linkages a plurality of lowermolecular weight organic radicals, all of said attached radicals being free from any benzene nucleus attached to the nitrogen by acyclic linkage.

6. A germ counteracting composition which comprises, as the essential germ counteracting ingredient thereof, a soluble quaternary ammonium compound, the ammonium nitrogen of which has a high molecular weight aliphatic radical, or not less than 14 nor more than 18 carbon atoms attached by a single valence and has attached by three of its valence linkages at least one lower molecular weight organic radical, at least one of said lower molecular weight radicals being acylated.

7. A. germ counteracting composition which comprises, as the essential germ counteracting ingredient thereof, a soluble quaternary ammonium compound, the ammonium nitrogen of which has a high molecular weight aliphatic radical, of not less than 14 nor more than 18 carbon atoms attached by a single valence and has attached by three of its valence linkages at least one lower molecular weight organic radical, at least one such lower molecular weight radical including a carbethoxy group.

8. A germ counteracting composition which comprises, as the essential germ counteracting ingredient thereof a soluble quaternary ammonium compound free from benzene nucleus and having attached to the ammonium nitrogen a cetyl radical and an acid ion constituent and the remaining valences of the ammonium nitrogen being attached to at least one organic radical the sum or the carbon atoms attached to said remaining vaiences is not more than 10.

9. A germ counteracting composition which comprises, as the essential germ counteracting ingredient thereof a soluble cetyl dimethyl carbethoxy methyl ammonium salt.

10. A germ counteracting composition which comprises an oleaginous base and, as the essential germ counteracting agent, a quaternary ammonium compound dissolved in said base, said compound being of the type in which R1, R2, R3 are lower molecular weight aliphatic radicals and R4 is a cetyl radical and X is an anion, said ammonium compound being dissolved in said oil base.

11. A composition as defined in claim 10, in which the oleaginous base is in emulsion in which the ammonium compound serves also as an emulsifying agent.

12. A composition as defined in claim 10, in which one of the groups R1, R2. R3, R4 is acylated.

13. A composition as defined in claim 10, in which one of the groups R1, R2, R3, R4 includes a -COOR group.

14. A germ counteracting composition which comprises, as the essential germ counteracting ingredient thereof, a soluble quaternary ammonium compound, the ammonium nitrogen of which has a high molecular weight aliphatic radical of not less than 14 nor more than 18 carbon atoms attached by a single valence and has attached by three of its valence linkages at least one lower molecular weight organic radical, at least one of said attached radicals being acylated.

ROBERT S. SHELTON.

CERTIFICATE OF CORRECTION.

Patent No. 2, 295,5ou.

September 191;.2.

ROBERT S. SHELTON It is hereby certified that error appears in the printed specification of the above numbered patent requiring correction as follows: Page 1, first 9 l 2, after the comma and before "including" ins germs";

page 2, first column, line 16, for the word "width" read -with and second column, line 25, for "weighth" read --weight--;

page 5, second column, line 55, for "cerium" read --serum-; page 5, second column, line that the said Letters Patent should be read with this correction therein that the same may conform to the record as, for "2 0" read --225--; and

of the case in the Patent Office. Signed and sealed this 12th day of January, A, D. 19L 5.

Henry Van Arsdale,

CERTIFICATE OF C ORRECTI ON Patent No. 2,295,504. September 8, 1914.2.

ROBERT s. SHELTON.

It is hereby certified that error appears in the printed specification of the above numbered patent requiring correction as follows: Page 1, first column, line 2, after the comma and before including insert germs--; page 2, first column, line 16, for the word "width" read "withand second column, line 25, for "weighth" read -weight; page 5, second column, line 55, for "serium" read -serum-; page 5, second column, line n6, for "250" read --22 and that the said Letters Patent should be read with this correction therein that the same may conform to the record of the case in the Petent Office.

Signed and sealed this 12th day of January, A. D. 1911.5.

Henry Van Arsdale 

